LIM proteins are a family of proteins that share a common structural domain. The LIM motif is so named because it was first described in three proteins from Drosophila melanogaster designated L, I, and M. The LIM motif is a cysteine-rich region with a characteristic pattern: [C-X-X-C-X.sub.17.+-.1 -H-X-X-C]-X-X-[C-X-X-C-X.sub.17.+-.1 -C-X-X-C]. LIM motifs form two loop structures and coordinate a zinc ion within each loop.
The LIM motif has been identified in a variety of proteins, including transcription factors, cytoskeletal proteins, and signaling molecules. LIM proteins are involved in cell fate determination, growth regulation, and oncogenesis. At least twenty-three members of the LIM family have been described, from nematodes to humans. Some LIM proteins consist of one, two, or three repeats of the LIM motif (LIM-only proteins). Others contain a LIM motif with a homeodomain (LIM-HD proteins) or a protein kinase domain (LIM-PK). LIM-PK inhibits the Ras oncogene-mediated differentiation of neural PC12 cells. LIM-HD proteins interact with DNA as well as bind to other proteins and are implicated in the control of differentiation of specific cell types. Studies in C. elegans demonstrated that LIM-HD proteins are involved in control of cell differentiation. Lin-11, a LIM-HD protein, controls the asymmetric cell divisions during vulval development, while Mec-3 is required for the differentiation of mechanosensory neurons. (Way, J. C. and Chalfie, M. (1988) Cell 54:5-16; and Freyd, G. et al (1990) Nature 344:876-879.)
The LIM-only proteins have not been shown to bind DNA, although the LIM structure is similar to the zinc finger, a well-characterized DNA-binding domain. LIM-only proteins include the rat cysteine-rich intestinal protein (CRIP), the human RBTN1 and RBTN2 proteins, and the chicken zyxin protein. (Higuchi, O. et al (1997) Oncogene 14:1819-1825; Sanchez-Garcia, I. and Rabbitts, T. H. (1994) Trends Genet. 10:315-320; and Dawid, I. B. et al (1995) C.R. Acad. III Sci. 318:295-306.) The genes for RBTN1 and RBTN2 are located on chromosome 11. Translocation mutations of chromosome 11 are associated with specific human T-cell acute leukemias. Transgenic expression of RBTN1 or RBTN2 produces leukemia and lymphoma in mice. (McGuire, E. A. et al (1992) Mol. Cell. Biol. 12:4186-4196; Fisch, P. et al (1992) Oncogene 7:2389-2397.)
A LIM-only protein known as PINCH protein (particularly interesting new Cys-His protein) was recently cloned from a human fetal liver library. PINCH protein contains five repeats of the LIM motif. Messenger RNA for PINCH protein is widely expressed, particularly in reproductive tissues, heart, and peripheral blood leukocytes. (Rearden, A. (1994) Biochem. Biophys. Res. Commun. 201:1124-1131).
The discovery of a new human PINCH protein homolog and the polynucleotides encoding it satisfies a need in the art by providing new compositions which are useful in the diagnosis, treatment, and prevention of cancer and reproductive disorders.